Relapsing eosinophilic pneumonia in a patient with recurrent breast cancer receiving abemaciclib plus endocrine therapy.

This report presents the case of a 42-year-old Japanese woman with recurrent hormone receptor-positive breast cancer who developed eosinophilic pneumonia (EP) during treatment with abemaciclib combined with endocrine therapy. Seven years after a radical surgery and definite diagnosis of Stage I breast cancer, her cancer recurred with metastases to multiple organs. Initially treated with abemaciclib plus letrozole and goserelin for 3 months, she developed EP, which improved after the discontinuation of anti-cancer treatment and the administration of prednisolone. However, EP occurred again upon the reintroduction of endocrine therapy (i.e., letrozole and goserelin). It improved gradually with the suspension of endocrine therapy and the re-administration of prednisolone. This case underscores the need for further research into the prevention and management of EP in patients receiving abemaciclib with endocrine therapy for advanced breast cancer.

Effective treatment of inhaled corticosteroid and bronchodilator for "lymphocytic interstitial pneumonia" in primary Sjögren's syndrome.

We present a case of an 86-year-old woman who visited our hospital with a one-year history of exertional dyspnea (modified medical research council dyspnea scale; mMRC grade 2). Despite the absence of any smoking or dust exposure history, multiple cystic lesions were apparent in both lungs on her CT scan. We suspected Sjögren's syndrome-associated lymphocytic interstitial pneumonia (LIP) due to her additional symptoms of dry mouth and eyes. Her respiratory function test showed a restrictive disorder with a forced vital capacity (FVC) of 1.23 L (70.3 % predicted), forced expiratory volume in 1 s (FEV1) of 0.88 L, and FEV1/FVC of 71.5 %. The flow-volume curve showed a downward convex, suggesting peripheral airway obstruction. We initiated a daily inhalation treatment regimen comprising vilanterol 25 µg and fluticasone furoate 200 µg. One month later, at the follow-up visit, the clinical diagnosis of Sjögren's syndrome with LIP was made by positive SS-A and SS-B antibodies in the initial blood work, a Saxon test that confirmed decreased salivary secretion, and a confirmed diagnosis of dry eyes by her ophthalmologist. We noted improvement in FVC of 1.45 L (+17.8 %) and FEV1 to 0.99 L (+12.5 %) in the subsequent respiratory function test, along with alleviation of her symptoms. The present case represents the first report of LIP treated exclusively with inhaled corticosteroids and bronchodilators, highlighting a potential therapeutic approach, particularly for elderly patients vulnerable to immunosuppressive therapies.

Clinical features of relapsed connective tissue disease-associated organizing pneumonia.

BACKGROUND: Organizing pneumonia (OP) is recognized as a nonspecific lung injury response characterized histopathologically by the presence of intra-alveolar buds of granulation tissue. Most OP patients show excellent responses to corticosteroids, but relapse is frequently seen when corticosteroids are tapered or discontinued. Although several factors associated with relapse have been reported in cryptogenic OP (COP), the clinical features and risk factors associated with relapse in connective tissue disease-associated OP (CTD-OP) have yet to be fully understood. METHODS: We retrospectively reviewed data on 47 CTD-OP patients. We investigated the frequency of relapse and compared the clinical data between CTD-OP with and without relapse to clarify the risk factors for relapse. RESULTS: Eleven (23.4%) CTD-OP patients had relapses of OP during the study. In the multivariate analysis, no CTD treatment at OP diagnosis [O.R. 11.920, p = 0.012] and partial remission after steroid treatment [O.R. 35.944, p = 0.045] were independent risk factors for relapse. Among rheumatoid arthritis-associated OP (RA-OP) patients, partial remission after steroid treatment [O.R. 16.151, p = 0.047] and age at OP diagnosis [O.R. 0.899, p = 0.045] were independent risk factors for relapse. Most of the relapsed OP patients who were on no medication at OP diagnosis later developed CTD. CONCLUSION: CTD-OP patients with residual disease on HRCT after treatment and who had OP diagnosis preceding CTD diagnosis were more likely to have an OP relapse. During the clinical course of relapsed OP patients, it is necessary to pay attention to the onset of CTD.

A Case of Allergic Bronchopulmonary Aspergillosis With Failure of Benralizumab and Response to Dupilumab.

We report a case of a 68-year-old woman who was being treated for bronchial asthma and developed allergic bronchopulmonary aspergillosis (ABPA) that was unresponsive to benralizumab therapy but went into remission with dupilumab therapy. The patient presented with an exacerbation of dry cough and was diagnosed with ABPA based on new diagnostic criteria. Despite the attempted therapeutic intervention, the patient declined to use systemic corticosteroids due to concerns about potential side effects. Subsequently, itraconazole and benralizumab were administered, with temporary relief before relapse. Given the patient's refusal to continue itraconazole and benralizumab, dupilumab was administered as an alternative therapy, which resulted in significant improvement of both symptoms and imaging. Although the use of biological agents for ABPA lacks clear evidence, our results suggest that dupilumab may provide an effective therapeutic strategy.

Tezepelumab treatment for allergic bronchopulmonary aspergillosis.

An 82-year-old man had been diagnosed with asthma. He experienced repeated exacerbations requiring treatment with a systemic corticosteroid despite being treated with medications including high-dose fluticasone furoate/umeclidinium/vilanterol, montelukast sodium, and theophylline; treatment with mepolizumab was then initiated. The patient had been free from exacerbations for 15 months; however, he suffered from post-obstructive pneumonia and atelectasis secondary to mucoid impaction in the right middle lobe of the lung, accompanied by a productive cough, wheezing, dyspnea, and right chest pain. In addition to the development of mucus plugs, the levels of serum IgE specific to Aspergillus spp. became positive; a definite diagnosis of allergic bronchopulmonary aspergillosis (ABPA) was established. The patient underwent treatment with tezepelumab. Over 3 months, the mucus plugs and pulmonary opacities diminished gradually in parallel with the improvement in the control of asthmatic symptoms. Tezepelumab might provide a novel steroid-sparing strategy for the management of ABPA, although further studies are required.

Successful treatment of relapsing polychondritis with circumferential bronchial wall thickening including the tracheomembranous area with tumor necrosis factor-α inhibitor.

This is a case of a 55-year-old man who presented with cough and anterior chest pain. Tracheal biopsy confirmed the diagnosis of relapsing polychondritis (RP). Although the patient had circumferential bronchial wall thickening extending to the tracheomembranous area and was positive foRPR3-ANCA, he did not meet the diagnostic criteria for granulomatosis with polyangiitis. The patient was refractory to prednisolone + methotrexate + azathioprine and responded to adalimumab, a biologic tumor necrosis factor-α inhibitor effective in RP refractory cases. Herein, we report a rare case of RP with circumferential bronchial wall thickening extending to the tracheomembranous area.

The Prognostic Performance of Lung Diffusing Capacity in Preserved Ratio Impaired Spirometry: An Observational Cohort Study.

Purpose: Similar to chronic obstructive pulmonary disease (COPD), the diffusing capacity of the lung (DLCO) might be decreased and associated with poor prognosis in preserved ratio impaired spirometry (PRISm), a clinical entity as a prodromal phase of COPD. The aims of the present study were to evaluate the distributions of DLCO and to assess the association between DLCO and mortality among subjects with PRISm. Patients and Methods: We conducted an observational cohort study at the National Hospital Organization Fukuoka National Hospital. We classified the 899 patients ≥ 40 years of age with an assessment of DLCO into five groups based on spirometry: preserved spirometry, PRISm, mild COPD, moderate COPD, and severe/very severe COPD. The prevalence of low DLCO (< 80% per predicted) was compared among the five groups. Using PRISm patients with follow-up data, we further investigated the association of low DLCO with all-cause mortality. Results: The prevalence of low DLCO in the PRISm group (58.8%) was significantly higher than that in the preserved-spirometry group (21.8%), the mild-COPD group (23.5%), and the moderate-COPD group (36.0%) (all P < 0.01), and it was comparable to that in the severe/very severe-COPD group (63.2%). The results remained unchanged after adjusting for potential confounders. Among the PRISm subjects, the overall survival rate was significantly lower in the low-DLCO group than in the preserved-DLCO group (P < 0.01). The multivariable-adjusted hazard ratio (HR) for all-cause mortality was significantly higher in the low-DLCO group than in the preserved-DLCO group (HR = 10.10 (95% confidence interval 2.33-43.89)). Conclusion: Diffusing capacity was more impaired in PRISm subjects than in those with preserved spirometry or mild to moderate COPD. Regarding PRISm, low DLCO was a significant risk factor for all-cause mortality. Clinicians should assess DLCO in the management of PRISm to predict the future risk of overall death.

Acute exacerbation in antineutrophil cytoplasmic antibody-associated interstitial lung disease: Clinical features and risk factors.

BACKGROUND: Acute exacerbation (AE) is a life-threatening clinical event that occurs during the clinical course of idiopathic pulmonary fibrosis (IPF). Several studies have reported that AE also occurs in interstitial lung disease (ILD) other than IPF. However, the incidence, clinical features, risk factors for AE, and major causes of death in antineutrophil cytoplasmic antibody (ANCA)-associated ILD (ANCA-ILD) patients have not been well established. METHODS: We retrospectively reviewed the data of 54 ANCA-ILD patients and 304 IPF patients. We investigated the frequency of AE, post-AE prognoses, risk factors for AE, and major causes of death in ANCA-ILD patients. We also compared the data of ANCA-ILD with that of IPF. RESULTS: Fourteen (25.9%) ANCA-ILD patients and 84 (27.6%) IPF patients developed AE. The median survival times (MSTs) after AE in ANCA-ILD and IPF patients were 35.5 and 60 days, respectively (p = 0.588, log-rank test). In a multivariate analysis, the percentage of predicted forced vital capacity (%FVC) [O.R. 0.750 (95% CI 0.570, 0.986), p < 0.01] and serum C-reactive protein (CRP) [O.R. 2.202 (95% CI 1.037, 4.674), p < 0.01] were independent risk factors for AE. AE was the most frequent cause of death in ANCA-ILD and IPF patients. CONCLUSION: ANCA-ILD patients could develop AE, and the frequency of AE in ANCA-ILD is similar to that in IPF. AE is the most frequent cause of death in ANCA-ILD patients. A low %FVC and a high serum CRP level were independent predictive factors for AE in ANCA-ILD. The prognosis after AE in ANCA-ILD was poor, as it was in IPF.

Impact of extrapulmonary comorbidities on physical activity in chronic obstructive pulmonary disease in Japan: A cross-sectional study.

Physical activity, which can be affected by airflow limitation and extrapulmonary comorbidities, has been reported to be reduced in patients with chronic obstructive pulmonary disease, and reduced physical activity is associated with higher risks of exacerbation and mortality. The aim of the present study is to elucidate the comprehensive effect of extrapulmonary comorbidities on physical activity in Japanese patients with chronic obstructive pulmonary disease, of which evidence is lacking. We conducted a cross-sectional study with a series of tests, including lung function, physical activity, symptom scores, and parameters for comorbidities. Sixty outpatients with stable disease were enrolled, and the relationship between the parameters and physical activity was evaluated. Physical activity was assessed over 7 consecutive days using a triaxial accelerometer, which records total daily energy expenditure, step count, and walking time. Cardiovascular status was assessed via echocardiography, and pulmonary artery pressure was estimated using Doppler sonography. As to mental status, depression and anxiety were assessed using the Self-Rating Depression Scale and State-Trait Anxiety Inventory, respectively. Physical activity level was significantly correlated with step count, walking time, body mass index, lean body mass index, lung function, pulmonary artery pressure, depression, anxiety, and serum total cholesterol level. In a median regression model analysis, low lung function, low lean body mass index, depression, and low serum total cholesterol level were independently associated with decreased physical activity level. These findings suggest that physical inactivity is affected by multiple extrapulmonary factors, including skeletal muscle dysfunction, depressive symptoms, and nutritional state, in Japanese patients with chronic obstructive pulmonary disease.

Clinical features of acute exacerbation in rheumatoid arthritis-associated interstitial lung disease: Comparison with idiopathic pulmonary fibrosis.

BACKGROUND: Several studies have reported that acute exacerbation (AE), which occurs during the clinical course of idiopathic pulmonary fibrosis (IPF), also occurs in rheumatoid arthritis-associated interstitial lung disease (RA-ILD). However, the incidence, clinical features, and risk factors for AE, a major cause of death of RA-ILD patients, and the differences in clinical aspects of AE between RA-ILD and IPF have yet to be fully understood. METHODS: We retrospectively reviewed data on 149 RA-ILD patients and 305 IPF patients. We investigated the frequency of AE and compared the clinical data between RA-ILD with and without AE to clarify the risk factor for AE. We also compared the post-AE prognosis and cause of death between RA-ILD and IPF patients. RESULTS: Twenty-seven (18.1%) RA-ILD patients and 84 (27.5%) IPF patients developed AE. The median survival time (MST) after AE of RA-ILD and IPF was 277 days and 60 days, respectively (log rank, p = 0.038). In a multivariate analysis, hypoalbuminemia [odds ratio (O.R.) 0.090 (95%CI 0.011-0.733), p = 0.012] and % carbon monoxide diffusion capacity (%DLCO) [O.R. 0.810 (95%CI 0.814-0.964), p < 0.01] were independent risk factors for AE. AE was the most frequent cause of death of RA-ILD and IPF. CONCLUSION: RA-ILD patients could develop AE, and AE was not uncommon in RA-ILD or IPF. %DLCO and hypoalbuminemia were predictive factors of AE in RA-ILD. The prognosis after AE of RA-ILD was significantly better than that of IPF. The most frequent cause of death in RA-ILD and IPF was AE.

The association between transfer coefficient of the lung and the risk of exacerbation in asthma-COPD overlap: an observational cohort study.

BACKGROUND: Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) patients experience exacerbations more frequently than those with asthma or COPD alone. Since low diffusing capacity of the lung for carbon monoxide (DLCO) is known as a strong risk factor for severe exacerbation in COPD, DLCO or a transfer coefficient of the lung for carbon monoxide (KCO) is speculated to also be associated with the risk of exacerbations in ACO. METHODS: This study was conducted as an observational cohort survey at the National Hospital Organization Fukuoka National Hospital. DLCO and KCO were measured in 94 patients aged ≥ 40 years with a confirmed diagnosis of ACO. Multivariable-adjusted hazard ratios (HRs) for the exacerbation-free rate over one year were estimated and compared across the levels of DLCO and KCO. RESULTS: Within one year, 33.3% of the cohort experienced exacerbations. After adjustment for potential confounders, low KCO (< 80% per predicted) was positively associated with the incidence of exacerbation (multivariable-adjusted HR = 3.71 (95% confidence interval 1.32-10.4)). The association between low DLCO (< 80% per predicted) and exacerbations showed similar trends, although it failed to reach statistical significance (multivariable-adjusted HR = 1.31 (95% confidence interval 0.55-3.11)). CONCLUSIONS: Low KCO was a significant risk factor for exacerbations among patients with ACO. Clinicians should be aware that ACO patients with impaired KCO are at increased risk of exacerbations and that careful management in such a population is mandatory.

Impact of visceral fat on the prognosis of coronavirus disease 2019: an observational cohort study.

BACKGROUND: Clarification of the risk factors for coronavirus disease 2019 (COVID-19) severity is strongly warranted for global health. Recent studies have indicated that elevated body mass index (BMI) is associated with unfavorable progression of COVID-19. This is assumed to be due to excessive deposition of visceral adipose tissue (VAT); however, the evidence investigating the association between intra-abdominal fat and COVID-19 prognosis is sparse. We therefore investigated whether measuring the amount of intra-abdominal fat is useful to predict the prognosis of COVID-19. METHODS: The present study enrolled 53 consecutive cases of COVID-19 patients aged ≥ 20 years with chest computed tomography (CT) scans. The VAT area, total adipose tissue (TAT) area, and VAT/TAT ratio were estimated using axial CT images at the level of the upper pole of the right kidney. Severe COVID-19 was defined as death or acute respiratory failure demanding oxygen at ≥ 6 L per minute, a high-flow nasal cannula, or mechanical ventilation. The association of VAT/TAT with the incidence of progression to a severe state was estimated as a hazard ratio (HR) using Cox regression analysis. To compare the prediction ability for COVID-19 disease progression between BMI and VAT/TAT, the area under the receiver operating characteristic curve (AUC) of each was assessed. RESULTS: A total of 15 cases (28.3% of the whole study subjects) progressed to severe stages. The incidence of developing severe COVID-19 increased significantly with VAT/TAT (HR per 1% increase = 1.040 (95% CI 1.008-1.074), P = 0.01). After adjustment for potential confounders, the positive association of VAT/TAT with COVID-19 aggravation remained significant (multivariable-adjusted HR = 1.055 (95% CI 1.000-1.112) per 1% increase, P = 0.049). The predictive ability of VAT/TAT for COVID-19 becoming severe was significantly better than that of BMI (AUC of 0.73 for VAT/TAT and 0.50 for BMI; P = 0.0495 for the difference). CONCLUSIONS: A higher ratio of VAT/TAT was an independent risk factor for disease progression among COVID-19 patients. VAT/TAT was superior to BMI in predicting COVID-19 morbidity. COVID-19 patients with high VAT/TAT levels should be carefully observed as high-risk individuals for morbidity and mortality.

Association of serum antibodies against the Mycobacterium avium complex and hemoptysis: a cross-sectional study.

BACKGROUND: Hemoptysis is very common and can be life threatening in clinical practice for nontuberculous mycobacteria. The serum antibody against the Mycobacterium avium complex (MAC-Ab), the majority of nontuberculous mycobacteria species, is well known to reflect the activity of MAC lung disease; however, there is no study investigating the association between the MAC-Ab and hemoptysis in MAC patients. Therefore, we assessed whether the MAC-Ab is a good biomarker for hemoptysis among subjects with MAC lung disease. METHODS: This study was conducted as a five-year retrospective survey at the National Hospital Organization Fukuoka National Hospital. A total of 155 patients aged ≥20 years with MAC lung disease were enrolled and separated into seropositive and seronegative groups using the cutoff for MAC-Ab levels of 0.7 U/ml. The prevalence of hemoptysis and odds ratios for the presence of hemoptysis were estimated and compared between the groups. To investigate the linear trends in the relationship between MAC-Ab levels and hemoptysis, the subjects were classified into three groups using the tertile distribution of the MAC-Ab. RESULTS: The prevalence of hemoptysis was twice as high in the seropositive group than in the seronegative group (42.2 and 21.7%, respectively, P = 0.02). The multivariable-adjusted risk of hemoptysis was elevated in the seropositive group as compared with the seronegative group (odds ratio = 2.79 (95% confidence interval 1.15-7.44)). Likewise, when categorizing the subjects into three groups, the risk of hemoptysis increased with increasing MAC-Ab levels (P = 0.03 for trend). CONCLUSIONS: A positive MAC-Ab level was a significant risk factor for hemoptysis among patients with MAC lung disease. There were also positive trends in the association between the MAC-Ab titer and the likelihood of hemoptysis. Measuring the MAC-Ab may contribute not only to early detection of the risk of hemoptysis but also to early intervention with anti-NTM therapy and, as a result, to the prevention of hemoptysis in MAC patients.

Nintedanib treatment for pulmonary fibrosis after coronavirus disease 2019.

A 78-year-old Japanese woman with no smoking history suffered from near-fatal coronavirus disease 2019 (COVID-19) requiring four-week invasive mechanical ventilation, with subsequent radiological features of pulmonary fibrosis. Although methylprednisolone gradually improved her respiratory condition, her oxygenation and exercise tolerance had drastically deteriorated, necessitating high-flow nasal cannula oxygen therapy. In parallel with tapering systemic steroid, the patient was treated with nintedanib. Three months later, the patient was able to walk with a walking aid using oxygen at 4 L/min. The present case is an indication that nintedanib might provide a novel therapeutic approach for managing post-COVID-19 fibrosis, although further studies are warranted.

Prevalence of asthma with airflow limitation, COPD, and COPD with variable airflow limitation in older subjects in a general Japanese population: the Hisayama Study.

BACKGROUND: Elucidating the prevalence of asthma and chronic obstructive pulmonary disease (COPD) is important for designing a public health strategy. Recent studies have discriminated a phenotype of COPD with variable airflow limitation (COPD-VAL) associated with asthma-COPD overlap syndrome. Its prevalence remains uncertain. The age and occupational distributions in the town of Hisayama and in Japan are nearly identical. Each disease's prevalence was estimated for the town's residents. METHODS: In 2008, town residents (≥ 40 years) were solicited to participate in a health checkup. Individuals with abnormal spirometry (forced expiratory volume in 1s/forced vital capacity [FEV1/FVC]<70% and/or %FVC<80%) were recommended for further evaluations. Two pulmonologists in a blinded fashion reviewed their medical records, including bronchodilator reversibility. Individuals with airflow limitation were classified as having asthma, COPD, COPD-VAL, or other diseases. The prevalence of each disease was then estimated. RESULTS: A total of 2100 residents (43.4% of residents in the age group) completed spirometry. In 455 residents with abnormal spirometry, 190 residents had further evaluations, and the medical records of 174 residents were reviewed. The prevalence of asthma with airflow limitation, COPD, and COPD-VAL, were 2.0%, 8.4%, and 0.9%, respectively. The prevalence of COPD and COPD-VAL were higher in men and smokers than in women and never-smokers. The prevalence of COPD, but not COPD-VAL or asthma, increased with age. CONCLUSION: The prevalence of asthma with airflow limitation, COPD, and COPD-VAL were estimated in a population of residents (≥ 40 years) in Hisayama.

Cigarette smoke impairs phagocytosis of apoptotic neutrophils by alveolar macrophages via inhibition of the histone deacetylase/Rac/CD9 pathways.

Efferocytosis, which is the homeostatic phagocytosis of apoptotic cells, prevents the release of toxic intracellular contents and subsequent tissue damage. Impairment of efferocytosis was reported in alveolar macrophages (AMs) of patients with chronic obstructive pulmonary disease (COPD), a common disease caused by smoking. In COPD, histone deacetylase (HDAC) activity is reduced in AMs. We investigated whether the reduction of HDAC activity is associated with the impairment of efferocytosis. Murine AMs were collected by bronchoalveolar lavage and their ability to efferocytose apoptotic human polymorphonuclear leukocytes was assessed. Pre-treatment of AMs with cigarette smoke extract (CSE) or trichostatin A (TSA), an HDAC inhibitor, suppressed efferocytosis and CSE reduced HDAC activity. TSA inhibited the activity of Rac, a key mediator of efferocytosis. These TSA-induced impairments were restored by treatment of AMs with aminophylline, a potent activator of HDAC. To further elucidate the underlying mechanism, we explored a role of CD9 in TSA-induced impairment of efferocytosis. CD9 is a transmembrane protein of the tetraspanin family that facilitates the uptake of several pathogens and other material. TSA profoundly down-regulated the expression of CD9 on AMs. The expression of CD9 was partly down-regulated by the Rac inhibitor. Pretreatment with an anti-CD9 mAb or CD9 small interfering RNA inhibited efferocytosis, which was attributable to the reduced binding of AMs to apoptotic cells. These results suggest that smoking impairs efferocytosis via inhibition of HDAC/Rac/CD9 pathways. Aminophylline/theophylline is effective in restoring the impairment of efferocytosis and might have benefit for the treatment of patients with COPD.

Mast cells contribute to double-stranded RNA-induced augmentation of airway eosinophilia in a murine model of asthma.

BACKGROUND: Clinical studies showed the contribution of viral infection to the development of asthma. Although mast cells have multiple roles in the pathogenesis of allergic asthma, their role of in the virus-associated pathogenesis of asthma remains unknown. Most respiratory viruses generate double-stranded (ds) RNA during their replication. dsRNA provokes innate immune responses. We recently showed that an administration of polyinocinic polycytidilic acid (poly IC), a mimetic of viral dsRNA, during allergen sensitization augments airway eosinophilia and hyperresponsiveness in mice via enhanced production of IL-13. METHODS: The effect of poly IC on allergen-induced airway eosinophilia was investigated for mast cell-conserved Kit+/+ mice and -deficient KitW/KitW-v mice. The outcome of mast cell reconstitution was further investigated. RESULTS: Airway eosinophilia and IL-13 production were augmented by poly IC in Kit+/+ mice but not in KitW/KitW-v mice. When KitW/KitW-v mice were reconstituted with bone marrow-derived mast cells (BMMCs), the augmentation was restored. The augmentation was not induced in the mice systemically deficient for TIR domain-containing adaptor-inducing IFN-ß (TRIF) or interferon regulatory factor (IRF)-3, both mediate dsRNA-triggered innate immune responses. The augmentation was, however, restored in KitW/KitW-v mice reconstituted with TRIF-deficient or IRF-3-deficient BMMCs. Although leukotriene B4 and prostaglandin D2 are major lipid mediators released from activated mast cells, no their contribution was shown to the dsRNA-induced augmentation of airway eosinophilia. CONCLUSIONS: We conclude that mast cells contribute to dsRNA-induced augmentation of allergic airway inflammation without requiring direct activation of mast cells with dsRNA or involvement of leukotriene B4 or prostaglandin D2.

Effects of tiotropium on lung function in severe asthmatics with or without emphysematous changes.

The effects of tiotropium, an inhaled long-acting anti-cholinergic agent, on lung function were investigated in obstructed severe asthmatics with and without emphysematous changes despite maximal recommended treatments with high-dose of inhaled glucocorticoids and inhaled long-acting ß(2)-agonists. We conducted a double-blind, placebo-controlled study of an inhaled single-dose of tiotropium in 18 asthmatics with emphysema and 18 without emphysema in a crossover manner. The primary efficacy outcome was the relative change in forced expiratory volume in 1 s (FEV(1)) from baseline to 60 min, and the secondary outcome was a relative change in FEV(1) from baseline to 12 h. Subsequently, the patients were treated with tiotropium inhaled once daily for 12 weeks in an open label manner, and lung function and symptoms were evaluated. At baseline, patients with or without emphysema had a mean FEV(1) of 55.9% before tiotropium and 56.8% before placebo, or 77.4% before tiotropium and 77.6% before placebo of the predicted value and were taking a mean dose of inhaled glucocorticoids of 1444 or 1422 µg/day. Among patients with emphysema, the increase from baseline FEV(1) was 12.6 percentage points higher at 60 min after tiotropium than after placebo. Among patients without emphysema, the increase from baseline FEV(1) was 5.4 percentage points higher at 60 min after tiotropium than after placebo. Tiotropium resulted in improved lung function and symptoms in asthmatics with and without emphysema. These findings suggest that tiotropium will provide a new strategy for the treatment of bronchial asthma and of overlapping asthma and COPD.